Inherited tubulopathies: Viva

Branch 1: The diagnosis and its segmental basis

The candidate should recognise this as Gitelman syndrome. The combination of a hypokalaemic metabolic alkalosis, a normal or low blood pressure, salt craving, muscle cramps and a low serum magnesium points to an inherited salt-losing tubulopathy of the distal convoluted tubule. The hypomagnesaemia is the key discriminator from Bartter syndrome, and the candidate should state that Gitelman is caused by loss-of-function mutations in SLC12A3, which encodes the thiazide-sensitive sodium chloride cotransporter NCC on the apical membrane of the distal convoluted tubule. The inheritance is autosomal recessive. ^[1]

If the examiner asks which investigations would confirm the diagnosis, the candidate should propose measuring the renin and aldosterone, which are both raised in Gitelman from the secondary hyperaldosteronism, and the urine calcium-to-creatinine ratio, which is low in Gitelman. The candidate should then arrange genetic testing with a tubulopathy panel covering SLC12A3 and the Bartter genes to settle any overlap. The low urine calcium and the low serum magnesium together, with a high renin and aldosterone and a normal or low blood pressure, are almost pathognomonic before the genetics return. ^[2]

If pressed on the differential, the candidate should distinguish Gitelman from Bartter syndrome, which presents earlier and with hypercalciuria and nephrocalcinosis, and from Liddle syndrome, which presents with hypertension and suppressed renin and aldosterone. The candidate should mention diuretic abuse as a mimic that requires a urine diuretic screen, and chronic vomiting, which produces a hypochloraemic alkalosis but with a low rather than high urine chloride. ^[5]